Neurostimulation Enhanced by Digital Health: Interview with CEO of NeuroMetrix

April 4th, 2018 Medgadget Editors Exclusive, Medicine, Orthopedic Surgery, Pain Management

Neurostimulation has the capacity to stop pain signals from traveling up to the brain, but to mask the pain effectively and for long periods of time clinicians have turned to implants. That is because conventional TENS (Transcutaneous Electrical Nerve Stimulation) devices don’t have the strength and focus to comfortably quell pain in long intervals.

NeuroMetrix, a publicly traded company based in Waltham, MA, has developed technologies that overcome many of the limitations of TENS devices, allowing the firm’s main product, the Quell Wearable Pain Relief device, which we tested out a few years ago, to fight pain externally for hours at a time.

We had a chance to speak with the CEO of NeuroMetrix, Shai N. Gozani, M.D., Ph.D., about the company’s technology, what it offers to patients, and how it will be improved in the future. What follows is a transcript of our conversation.

Medgadget: How does the device work, what’s the technology behind the device?

Shai N. Gozani M.D., Ph.D.: At its core it’s neurostimulation. Broadly, it’s in a category of TENS devices. What we’ve tried to do, when you think in terms of the spectrum of neurostimulation from short-term TENS devices all the way to implantable spinal cord stimulators, they all operate on a similar principle of activating the descending pain inhibition system, but there is a huge difference in dose. The typical TENS devices are put on for a very short period of time. Not stimulating a lot of nerves, very low dose, you’re going to get maybe some localized effect. Implantables are 24×7, stimulating a large surface area, because they are at the dorsal column of the spinal cord at the proximal location. What we try to do is trying to achieve a much higher dosing but non invasively, so the model is a wearable chronic use device.

It’s a nerve stimulator, worn with a large electrode, so you stimulate a lot of nerves. Not as much of a surface area as you effectively get with implantables, but a large large surface area. It’s designed to be a wearable, including during sleep, so our average user gets about 10 hours of wear per day. So very dramatically different level of dosing, because essentially, nerve stimulation is like a short acting analgesic. It’s effective when you are stimulating, it’s not effective when you are not stimulating. So, to combat chronic pain, which is going to be there most of the time, you really need something that is stimulating nearly continuously, but only so many people are going to get an implantable. There is a cost, side effects, and other downsides to getting an implantable. We think there is a huge number of people that can benefit from regular neurostimulation, but not with an implantable. And that’s where we try to come in.

It’s leveraging what is believed to be the same mechanism of [pain control], which is intense stimulation of sensory nerves to up-regulate descending inhibition, thereby reducing pain. It has an analgesic effect. Probably at the frequencies we are using it seems to be more enkephalin-based, so delta opioid receptors than endorphin or mu receptors. And the advantage of that is, of course, if they are on opioids, those are mu receptor agonists, so it may work with people that are somewhat already desensitized due to chronic opioid use. We don’t really have that data. Others have done these kinds of studies, so it’s at least a theory, but it’s an interesting idea. And that’s basically the principle. It’s designing a wearable, to give chronic stimulation non-invasively.

Now, because we are on the body for such prolonged periods of time, we are also monitoring. We have an accelerometer so we can monitor various aspects of sleep. We monitor activity, we monitor [walking] gait and gait characteristics such as variability and stride. All these are biomarkers of chronic pain. All this data is aggregated by the device and sent to the app. The app then allows you to enter subjective information, like pain levels, interference of pain with quality of life, mood, sleep. Then all this data is integrated and sent up to the cloud where we are starting to do more and more data analytics on that.

What can we learn about you and how you use our product and you pain profile? We also collect your pain characteristics, your diseases, your demographics. And we are trying now to say, “OK, see, you are using it this way. Can I, based on comparing you to other people who are getting maybe better results, can I suggest some ways for you to improve the utilization of the device?” So we are trying to close the loop.

You don’t use our product to monitor your sleep activity or gait. You use our product to get pain relief. But because we are already on-body we can then collect data to hopefully can make it even more effective for you. We already have about 50,000 contributors to our database, making it one of the largest chronic pain databases around. Maybe the largest, I don’t know, hard to tell. So we are getting tremendous insight now about who benefits from our product, their characteristics. We’ve learned a lot. Our average user has multi-site pain, which is not uncommon. So, it’s typically 3-4-5 sites of pain, which is becoming more and more prevalent. They typically have three different kinds of conditions. For example, they have arthritis, they have back pain, and diabetes. Really, pretty sick patients. They have everyday pain. We know how much pain they have, how much it effects different aspects of life. Really, it’s a lot of insights. It’s really a neurostimulator that is enhanced by digital health. And we think this combined synergy is really going to lead us to better intervention that neurostimulation alone. Because it becomes smarter. I don’t just blast you with electrical stimulation, I am trying to blast you with right kind of electrical stimulation at the right time.

The device is also highly personalizable. For example, people have circadian rhythms in their pain levels. Some people have more pain in the mornings, others have more pain at night. For example, diabetics have more pain at night due to neuropathy. Fibromyalgia patients tend to have more pain in the morning. Our device can become smarter due to that, it can automatically adjust to circadian distribution of pain and give you more in the morning and less at night, or vice versa, whatever you need. So you can get smoother pain behavior, better experience over the course of your day. That’s the personalization aspect of the device that we also include.

Medgadget: So there is evidence out there that circadian variability affects pain?

Dr. Gozani: Oh yes! There is diurnal variability. People with neuropathic pain, particularly diabetics with neuropathy, their pain gets much much worse in the evening. It’s why they have such bad sleep. Fibromyalgia patients tend to wake up with a lot of pain. It tends to be worse in the morning. There are circadian variations in body temperature, in hormones, in other physiological behaviors, and how it all interacts with pain modulating molecules. All the pain modulating molecules are circadian. They go up and down in the course of the day. The autonomic system is highly influential in your regulation of pain. Your cardiovascular parameters regulate pain. They go up and down in the course of the day. All these things interact, so it’s not surprising that you see this variation. It’s not necessary a dominant effect, but if your pain is really bad at night, it prevents you from going to sleep. If your pain is bad in the morning, maybe it prevents you from going to work. So these things could be really important in terms of influencing other aspects of your life.

Medgadget: How is your device different from TENS?

Dr. Gozani: Really, I would go back to dose. It’s designed to deliver a much higher dose. Say, I play too much tennis, my elbow hurts. A typical device delivers localized pain relief. We are not trying to do that. We trying to down regulate pain perception on a wide-spread basis. And to do that you have to stimulate chronically for long periods of time at high frequency. So it’s designed from the ground up: battery power, stimulation energy, frequency, wearability to be used 10 hours a day. That is a very challenging task. Even in terms of battery life: if you have to charge it every four hours, it’s not usable. So we get once a week charging by using a very high power, high capacity lithium polymer battery and very very efficient ways of stimulating the nerves to activate it with least amount of power. Because you got to go for long periods of time.

So, it’s not as much science as it’s engineering. The principle of neuro stimulation for pain regulation is what? 40-50 years? Neuro stim has been around for a long time. TENS was originally designed as a screening device for implantables. If you respond to neurostim non-invasively, then we’ll put in the implantable. What they saw is actually people responding to non-invasive stimulation. And that started the TENS industry. The problem with TENS devices is that they are so underpowered. And they are used for such a short periods of time that they are not going to give you much of an effect, other than where they are stimulating. The implantables are on 24×7, they are on the dorsal column or dorsal root, so they are stimulating many dermatomes. That’s a strong input. So we are trying to get in there, we are trying to be close to that but with much different technology. It’s not invasive. We now have clearance to sell it directly to consumers. $250 instead of $2500, and there is no surgical risk. That’s what different: it’s the dosing, but to do it, you need to design from the ground up for that purpose.

Medgadget: What are the main indications?

Dr. Gozani: The common forms of chronic pain: neuropathic pain, lower back pain, arthritic pain particularly in the lower extremities, fibromyalgia. Those are big uses. We’ve done studies in cancer pain. We’ve done studies in chemotherapy-induced peripheral neuropathy. We’ve done a lot of studies to see in different areas. I have to say it does not work for migraines and headaches. Which is really a different physiology than traditional peripheral pain. What we find is that efficacy is more about individual variability than disease variability. So, you and I might be responding to it and we might have very different conditions, but another person with the same condition as you might not have the same response. Individual genetics, physiological makeup, and social and behavioral and psychological response to pain: some people are responsive to the stimulation, and some just aren’t. This is true for any kind of neurostimulation, but it’s also true for analgesics. It’s just one of the big challenges in pain medicine.

Medgadget: Concluding thoughts?

Dr. Gozani: We are very excited. We are three years into it. The first year was 2015. We launched at CES. We shipped 14,000 devices in the first year. Last year we shipped over 80,000 devices. So we’ve grown rapidly. We sell the product different ways. We do TV and online advertising. We sell e-commerce: Amazon and on our website. We also do retail: CVS and BestBuy are our two biggest ones. And we do TV, like QVC. We also sell through doctors: we sell through pain medicine physicians, neurologists, sleep centers, but the bulk is direct to consumer. And it’s kind of interesting: people with chronic pain are searching for solutions, they don’t want to be dependent, so they are out there on the internet and listening, and trying to find alternatives, so if you can get in front of them, they’ll give you a chance.